Background: The goal of phase 3 randomized clinical trials (RCTs) is to show clinically meaningful benefit for patients. An analysis of phase 3 RCTs presented at the ASCO 2022 Annual Meeting (ASCO22) was undertaken to assess which endpoints were evaluated. Methods: A systematic analysis was undertaken of ASCO22 abstracts from phase 3 RCTs reporting primary, secondary, interim, updated, and subgroup analyses, as well as trials reporting methodology of currently enrolling studies. Trials that reported posthoc, exploratory, biomarker, and retrospective analyses of RCTs were excluded. Information from ASCO22 materials and clinical trial registration websites was recorded by two independent researchers. Results: In total, 166 RCTs were identified: 93 trials with 50,781 enrolled patients and 73 trials expected to enroll 52,098 patients. More trials reported on patients with locally advanced/metastatic cancer (64.5%) compared to localized cancer (35.5%). Funding source was pharmaceutical or biotechnology company in 62%. Within locally advanced/metastatic trials, overall survival (OS) was a primary endpoint in 40%, while progression-free survival (PFS) was a primary or co-primary endpoint in 45% and 13% respectively. Other primary endpoints included (invasive) disease-free survival ((i)DFS), event free survival (EFS), overall response rate and pathological complete response. In trials that did not include OS as a primary endpoint, OS was a secondary endpoint in 88% (n = 56/64). Within the localized group, trials were subdivided into adjuvant, neo-adjuvant, definitive and other categories. Within the adjuvant trials (n = 27), the most common primary endpoint was (i)DFS (37%), followed by OS (15%). Other primary endpoints included recurrence-free survival, invasive breast cancer free survival, metastasis-free survival, EFS, and PFS. Across all trials, quality of life (QOL) was never reported as a primary endpoint, however it was as a secondary or other outcome in 53% for locally advanced/metastatic trials and 42% for localized trials. When comparing the endpoints reported in the ASCO22 abstract and meeting materials with those listed on the trial registration website, discordance was noted in 14%. Conclusions: Phase 3 RCTs presented at ASCO22 represented participation from over 100,000 patients, however, fewer than half in locally advanced/metastatic cancer and fewer than one quarter in localized disease utilized OS as a primary endpoint. QOL was listed as an endpoint in roughly one half of all trials. Endpoints reported did not match registration data in a significant minority. Debate over which endpoints should be used for cancer RCTs should be informed by this data.